Parenteral Nutrition in the Treatment of Acute Pancreatitis: Effect on Complications and Mortality JOHN T. GOODGAME, M.D.,* JOSEF E. FISCHER, M.D.
Clinical characteristics of 46 cases of acute pancreatitis treated with total parenteral nutrition were examined. Hyperalimentation may be used in these severely ill patients with minimal technical or metabolic morbidity. This method of nutritional support can maintain patients with nonfunctional gastrointestinal tracts for several months. Catheter-related sepsis was more common than expected early in the course of acute pancreatitis but caused minimal morbidity. The incidence of catheter-related sepsis late in disease was minor. Hyperalimentation had little if any effect on the pathophysiology of acute pancreatitis as judged by the overall mortality and the incidence and severity of the complications of acute respiratory failure and acute renal failure. It is not clear that parenteral hyperalimentation alters the course of acute pancreatitis but it is a useful adjunct for nutritional support in this illness.
THE THERAPY OF PANCREATITIS is basically sympto-
matic and empiric as the fundamental etiology of the disease is unknown. Suggestions of potentially beneficial modalities are made as new features of the disease or of pancreatic excretory function are elucidated. Specifically, glucagon,14 trasylol,26 diamox,19 atropine,16 antibiotics16 and steroids4 have all been acclaimed as helpful, or even life-saving, in acute pancreatitis. Subsequently, most have been questioned as non-contributory to the ultimate outcome of the disease. 18,24 Emphasis on adequate nutrition as a cornerstone of adequate surgical therapy is relatively recent. As methods of nutritional support in severe illness have become more readily available, evaluation of the usefulness in various conditions has become essential. The alternatives for nutritional support are oral feedings, feedings via indwelling intestinal conduits such as gastrostomy or jejunostomy tubes, and parenteral nutrition. In pancreatitis, because of the usually associated ileus and the desire to keep the G.I. tract and pancreatic exocrine system in a state of "rest," nutritional maintenance by means of the G.I. Current address: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20014. Submitted for publication: August 26, 1976. *
651
From the Hyperalimentation Unit, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
tract is difficult. The concomitant problems of sepsis, metabolic abnormalities, and potential cardiovascular instability mitigate against plans for nutritional supplementation with glucose-rich hyperosmolar fluids administered via indwelling polyethylene catheters. Attention has recently been focused by Feller et al.6 on the value of nutritional support in the treatment of "severe pancreatitis". They partially attribute a reduction of overall mortality from 22% to 14% to their ability to correct nutritional depletion via hyperalimentation. This report reviews our experience and discusses the relationship of hyperalimentation to the complications of pancreatitis. It is to be emphasized that the retrospective nature ofthis analysis and the absence of any true control group makes definitive conclusions difficult. Qualitative assessment ofthe risk-benefit ratio is our present objective. Table 1 summarizes some of the published experiences of other groups with acute pancreatitis, with specific reference to the complications and mortality, and will serve as a baseline for discussion.
Materials and Methods The clinical records of patients with the diagnosis of acute pancreatitis who were treated with parenteral nutrition during the 36 month period between January 1972 and December 1974 were reviewed. The 44 patients required 46 admissions for acute pancreatitis and represent 11% of all patients admitted with the diagnosis of acute pancreatitis during that time period. Criteria for inclusion in the study were as follows: (1.) All patients were hyperalimented during the period of time in which they had clinical pancreatitis. (2.) Significant oral intake had been omitted for at least
Ann. Surg. * November 1977
GOODGAME AND FISCHER
652
TABLE 1. Complications of Acute Pancreatitis in Selected Published Series Renal Failure Author Present study
Gordon'0 Interiano'3 Gleidman" Feller" Frey8
Ranson2l Lawson'5
Total Number of Patients and Selection Factor
Overall Mortality
46 (severe pancreatitis) 41 (unselected) 50 (unselected) 26 (malignant pancreatitis) 83 (severe pancreatitis) 306 (unselected) 31 (severe pancreatitis) 15 (severe pancreatitis)
9/46 (20%) 6/41 (15%) 5/50 (10%) 9/26 (35%) 12/83 (14%) 78/306 (259'o) 15/31 (48%) 4/15 (26%)
Study Population The study population is heterogeneous. The statistical profile of etiologies, underlying medical diseases, and management modalities places it on the "severe" end of the spectrum of acute pancreatitis. For many reasons the group of patients studied is heavily weighted toward that sub-group of acute pancreatitis which is handled surgically, and does not
Biliary Alcohol Traumatic
Hyperlipoproteinemia (Type IV) Postoperative Carcinoma of Pancreas Idiopathic
Died
Total
15 8 5 2 3 1 3
3 1 1
18 (39%) 9 (20%) 6 (13%) 2 ( 4%) 3 ( 7%) 2 ( 4%) 6 (13%)
1 3
Mortality
Incidence
7/46 (15%) 6/41 (15%)
4/7 (57%) 3/6 (50o)
13/46 (28%) 8/13 (62%) 9/50 (18%) 5/9 (55%)
19/306 (6%) 10/31 (32%)
Studies
Survived
Mortality
Incidence
18/83 (22%) 8/18 (44%)
4-5 days prior to use of parenteral nutrition. The diagnosis was established by each patient meeting at least two of the following three criteria: (1.) A clinical syndrome of abdominal pain and/or vomiting and epigastric tenderness (46 out of 46 patients). (2.) Increased serum level of amylase greater than 25 Russell units or lipase greater than one unit/ml (43 out of 46 patients) and/or increased ratio of amylase clearance to creatinine clearance (17 out of 29 patients).27 (3.) Operative or pathologic findings consistent with the diagnosis of acute pancreatitis (37 out of 46 patients). Of the 44 patients studied, 21 were male and 23 were female. Their age range was from 8 to 90 years. There were 10 patients treated in 1972, 17 in 1973, and 17 in 1974. The details of the composition of the parenteral hyperalimentation solutions and administration have been described elsewhere.1 7'22 Six patients with renal failure complicating their hospital course were treated with essential amino acids and hypertonic dextrose.1
TABLE 2. Mortality by Etiology of Pancreatitis
Respiratory Failure
18/19 (95%) 6/10 (60o)
12/31 (39o) 9/12 (75%)
Surgical Mortality
8/36 (22%) 9/16 (56%) 36/211 (17%) 10/21 (48%) 4/16 (26%)
illustrate a representative cross-section of the patients who present with pancreatitis. Our experience overall has been that approximately 70o of those with acute pancreatitis have alcohol ingestion as the principal underlying etiologic agent and 80%o have no operative intervention during their hospital course. The large percentage of patients in this series treated operatively does not suggest differences in indications for operative intervention as much as selection of patients for hyperalimentation because of the relative severity of their illness. Biliary tract disease was the etiology of pancreatitis in 39% (18 of 46 of our patients), alcohol in less than 20% (6 of 46). Postoperative pancreatitis (three of 46) followed caesarian section, transduodenal sphincteroplasty for recurrent common duct stones, and excision and grafting of an abdominal aortic aneurysm. Carcinoma of the pancreas (two of 46) presented with the syndrome of recurrent epigastric pain, elevated pancreatic enzymes and volume requirement. Laparotomy was required in both cases to establish the diagnosis. The category of traumatic pancreatitis (6 of 46) might well be considered with the postoperative group as all required emergency surgery after their primary injury. Pancreatitis persisted in the postoperative course but in all 6, was thought etiologically related to the trauma. All 6 initial procedures were for control of intraabdominal bleeding but two involved repair of a pancreatic laceration and one distal pancreatectomy. The contribution of etiology of pancreatitis to ultimate mortality is illustrated in Table 2. Four of the 46 patients in this group had uncomplicated past medical histories. The vast majority had complicating underlying illnesses which further jeopardized their survival capacity when faced with the stress of acute pancreatitis. These concomittant medical problems are summarized in Table 3. Management
Non-Operative The multiplicity of modalities which exist for the therapy of pancreatitis was reflected in the various
Vol. 186. No. 5
653
PARENTERAL NUTRITION IN PANCREATITIS
regimens used in these patients. All but two had nasogastric tubes placed (44 out of 46). Seventy per cent of the patients were placed on "6prophylactic" antibiotics. The choices of specific agents reflected an attempt at broad spectrum coverage and included various regimens. Ampicillin or cephalothin was used alone in 18 patients. In 8 additional cases the combination of penicillin and chloramphenicol or clindamycin and an aminoglycoside was chosen. No statement can be made as to the incidence of septic complications with these regimens but certainly none of the antibiotic umbrellas completely prevented wound infection or septicemia in these patients. Volume requirement was dealt with appropriately with heavy reliance on colloid. Seventy-four per cent of these patients required blood transfusions during the course of their illness. Forty-one per cent received two to 10 units while 20o received greater than 10 units of blood. Salt poor albumin and furosemide were used in 6 patients with pulmonary edema and pancreatitis but results were equivocal. Two patients seemed to respond rapidly to this regimen but two resolved their pulmonary problems over 5-7 days and two clearly deteriorated on this therapy. Cardioactive drugs were used in 25% of all patients for complications of low cardiac output. Digitalization was carried out acutely in 8 patients and 7 required vasoactive amines to maintain their cardiac output. One patient was treated for a brief period with an intra-aortic balloon pump with TABLE 3. Associated Medical Problems at Time of Presentation with Pancreatitis (46 Patients)
Cardiovascular Disease (including angina, valvular disease and arrythmias requiring outpatient medication) Pulmonary Disease COPD Pneumonia Pleural effusion Active TB
Acute/Chronic Alcoholism Delirium Tremens
Significant Liver Disease Biopsy confirmed cirrhosis Viral hepatitis Status-post portocaval shunt Significant Renal Disease (BUN > 36, Creatinine > 2.0) Anuria Other Duodenal ulcer Cerebrovascular 5 disease accident Diabetes Mellitus 5 Sjogren's Syndrome with cryoGI bleeding globulinemia Porphyria Multiple Sclerosis
6 3
2 I
12 2
3
2
TABLE 4. Operative Procedures During Hospital Course for Pancreatitis Survival by Procedure
GU reconstruction and small bowel resection 3-Tube placement (15) External drainage of pancreatic pseudocyst or abscess Distal pancreatectomy Cholecystectomy Cholecystostomy CDE Pancreatic cystogastrostomy Splenectomy Puestow procedure Transduodenal sphincterotomy and sphincteroplasty Dilatation of papilla Repair of pancreatic laceration By-pass procedure for pancreatic carcinoma
No. of Patients
Survived
Died
1 9
1 4
0 5
8 3 11 3 11 6 1 2
4 3 9 2 9 1 1 2
4 0 2 1 2 5 0 0
0 1 1
7 1 0
1 0 1
2
2
0
initial success in dealing with cardiac dysfunction only to fall victim to late cardiac arrest. Large doses of corticosteroids were given to three patients whose initial course suggested a septic component to their presenting shock (two of the three patients survived). Peritoneal dialysis was used in the therapy of 6 patients and atropine was used in only one. Glucagon and trasylol were not used in any of the patients in this series. There were 10 patients (22%) who were treated completely nonoperatively. In this sub-group there was only one death. The immediate cause of death of this patient was acute renal failure and intractable cerebral edema. Operative Treatment Indications for operation in these cases of acute pancreatitis were: (1) Deterioration or failure to improve on an
"optimal medical program". (2) Clinical
suspicion of biliary disease, pancreatic carcinoma or pancreatic pseudocyst/abscess as the etiology of the acute pancreatitis. (3) Complication of the course of acute pancreatitis with sepsis from an apparent intraabdominal source or intra-abdominal bleeding. (4) Therapy of relapsing pancreatitis. Because of the variability of intra-abdominal pathology, the clinical setting and individual experience, multiple procedures were often required at a single operative venture. The variety and frequency of these procedures is illustrated in Table 4. Six patients had two operations during the course of their hospital stay with four requiring redrainage of intra-abdominal abscesses, one requiring re-exploration for bleeding
GOODGAME AND FISCHER
654 15r
Iz
Ann. Surg.
November 1977
* Total Number of Patients Ea Number of Patients Dying After This Period of TPN
10F FIG. 1. Duration of G.I. dysfunction and inability to take oral nourishment as indicated by duration of parenteral nutrition had no effect on the mortality of the illness.
LA.
0
z
9
5F
u
n1
1-10
11-20
21-30
31-40
Ifl I|
In
51-60 DAYS OF TPN
61-70
41-50
immediately postoperatively, and one requiring a gastrojejunostomy for chronic duodenal obstruction secondary to pancreatitis. Of these 6 patients, two died and four were discharged. Of the total operative group of 36 patients, eight (22%) died and 28 (77%) were discharged. Of the 8 patients who died, two died in intractable septic shock, two died of combined cardiac, pulmonary and renal failure, and one succumbed to an acute myocardial infarction secondary to septic hypotension following a T-tube cholangiogram. The other three patients died of pulmonary embolism, pulmonary insufficiency, and acute renal failure with terminal candida sepsis. Hyperalimentation and Hospital Course
Despite the overall severity of acute pancreatitis and the multiplicity of underlying medical problems in this group, the technical features of hyperalimentation offered few problems. Ninety-nine catheters were placed with only three mechanical complications. There was one episode of subclavian artery puncture which required no specific therapy and one episode of subcutaneous infiltration of hyperalimentation solution secondary to inadequate fixation of the administration catheter. Neither of these complications added to inhospital time. One patient developed subclavian vein thrombosis noted two weeks after discharge after complaints of arm swelling prompted a venogram. This required 6 weeks of anticoagulation for resolution. Duration of hyperalimentation varied from five to 90
I
71-80
81-90
days with an average of 28 days per patient. When the 46 patients are divided into two groups according to the length of time they required parenteral nutrition (Fig. 1), those who were unable to eat for more than one month did no worse in terms of survival than those whose disease resolved in less than 30 days. Much of this similarity may be explainable on the basis of more severe disease present in those who died early in their course, but nutritional support certainly contributed to the progress of the group of severely ill patients unable to take oral alimentation for 50 to 90 days. Parenteral nutrition was discontinued after oral intake was adequate in 33 of the 46 patients studied. Five patients were hyperalimented until their death and two patients had their I.V. nutrition discontinued when hope for their recovery was lost. Six patients had their hyperalimentation discontinued because of complications directly related to that modality of therapy. Episodes of catheter-related sepsis prompted discontinuation in five patients while inability to control rising serum potassium was given as the reason for stopping parenteral nutrition in one other. Despite the relative metabolic chaos resulting from pancreatitis itself and the 15% incidence of acute renal failure, there were only four episodes of metabolic abnormalities which required discontinuation of hyperalimentation. Initial glucose intolerance was common (25%) but was usually controlled by temporarily reducing the infusion rate or by incorporating small amounts (10-20 units) of regular insulin to the infusion mixture. There was only one patient in whom glucose
Vol. 186 . No. 5
PARENTERAL N UTR1I TIO N IN PANCREATITIS -
.
.
v.
I.,
-
-
-
intolerance posed a significant problem. This eventually required 60 units of regular insulin per liter of hyperalimentation solution to maintain a blood glucose of less than 200 mg per 100 milliliters. There were two episodes of protein intolerance with elevation of serum ammonia. One episode occurred in a patient with a previous portacaval shunt. The second occurred in a patient with persistent bacteremia secondary to undrained intra-abdominal abscesses who finally succumbed to cardiovascular collapse related to her prolonged sepsis. Electrolyte abnormalities were common in this population but usually responded to manipulation of the content of the hyperalimentation mixtures. Of particular interest was hypocalcemia ( 50, Creatinine > 3.5, urine output 75 with normal creatinine & urine output)
2
Metabolic
New onset glucose intolerance requiring insulin
Hyperammonemia Hypokalemia Hypocalcemia Encephalopathy Surgical Complications (36 patients required operation) Wound infections Wound dehiscence Recurrent intrabdominal abscess Fistulas Re-exploration for bleeding Duodenal obstruction requiring reoperation post-sphincteroplasty Bleeding Dyscrasia
7 2 1 7 1
3 1 1 1 -
16 13 2 4 3 1
4 3 3 1
2
18% to 39o. The mortality associated with this complication ranges from 44% to 75%. There is no improvement in these parameters in this series of hyperalimented patients with an incidence of respiratory failure of 28% and a mortality associated with this complication of 62%. Renal abnormalities affected 9 patients and ranged from simple pre-renal azotemia in two patients, to acute renal failure (BUN >50, creatinine >3.5, urine output
Clinical characteristics of 46 cases of acute pancreatitis treated with total parenteral nutrition were examined. Hyperalimentation may be used in these severely ill patients with minimal technical or metabolic morbidity. This method of nutritional support can maintain patients with nonfunctional gastrointestinal tracts for several months. Catheter-related sepsis was more common than expected early in the course of acute pancreatitis but caused minimal morbidity. The incidence of catheter-related sepsis late in disease was minor. Hyperalimentation had little if any effect on the pathophysiology of acute pancreatitis as judged by the overall mortality and the incidence and severity of the complications of acute respiratory failure and acute renal failure. It is not clear that parenteral hyperalimentation alters the course of acute pancreatitis but it is a useful adjunct for nutritional support in this illness.
THE THERAPY OF PANCREATITIS is basically sympto-
matic and empiric as the fundamental etiology of the disease is unknown. Suggestions of potentially beneficial modalities are made as new features of the disease or of pancreatic excretory function are elucidated. Specifically, glucagon,14 trasylol,26 diamox,19 atropine,16 antibiotics16 and steroids4 have all been acclaimed as helpful, or even life-saving, in acute pancreatitis. Subsequently, most have been questioned as non-contributory to the ultimate outcome of the disease. 18,24 Emphasis on adequate nutrition as a cornerstone of adequate surgical therapy is relatively recent. As methods of nutritional support in severe illness have become more readily available, evaluation of the usefulness in various conditions has become essential. The alternatives for nutritional support are oral feedings, feedings via indwelling intestinal conduits such as gastrostomy or jejunostomy tubes, and parenteral nutrition. In pancreatitis, because of the usually associated ileus and the desire to keep the G.I. tract and pancreatic exocrine system in a state of "rest," nutritional maintenance by means of the G.I. Current address: Surgery Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, 20014. Submitted for publication: August 26, 1976. *
651
From the Hyperalimentation Unit, Department of Surgery, Massachusetts General Hospital, Boston, Massachusetts
tract is difficult. The concomitant problems of sepsis, metabolic abnormalities, and potential cardiovascular instability mitigate against plans for nutritional supplementation with glucose-rich hyperosmolar fluids administered via indwelling polyethylene catheters. Attention has recently been focused by Feller et al.6 on the value of nutritional support in the treatment of "severe pancreatitis". They partially attribute a reduction of overall mortality from 22% to 14% to their ability to correct nutritional depletion via hyperalimentation. This report reviews our experience and discusses the relationship of hyperalimentation to the complications of pancreatitis. It is to be emphasized that the retrospective nature ofthis analysis and the absence of any true control group makes definitive conclusions difficult. Qualitative assessment ofthe risk-benefit ratio is our present objective. Table 1 summarizes some of the published experiences of other groups with acute pancreatitis, with specific reference to the complications and mortality, and will serve as a baseline for discussion.
Materials and Methods The clinical records of patients with the diagnosis of acute pancreatitis who were treated with parenteral nutrition during the 36 month period between January 1972 and December 1974 were reviewed. The 44 patients required 46 admissions for acute pancreatitis and represent 11% of all patients admitted with the diagnosis of acute pancreatitis during that time period. Criteria for inclusion in the study were as follows: (1.) All patients were hyperalimented during the period of time in which they had clinical pancreatitis. (2.) Significant oral intake had been omitted for at least
Ann. Surg. * November 1977
GOODGAME AND FISCHER
652
TABLE 1. Complications of Acute Pancreatitis in Selected Published Series Renal Failure Author Present study
Gordon'0 Interiano'3 Gleidman" Feller" Frey8
Ranson2l Lawson'5
Total Number of Patients and Selection Factor
Overall Mortality
46 (severe pancreatitis) 41 (unselected) 50 (unselected) 26 (malignant pancreatitis) 83 (severe pancreatitis) 306 (unselected) 31 (severe pancreatitis) 15 (severe pancreatitis)
9/46 (20%) 6/41 (15%) 5/50 (10%) 9/26 (35%) 12/83 (14%) 78/306 (259'o) 15/31 (48%) 4/15 (26%)
Study Population The study population is heterogeneous. The statistical profile of etiologies, underlying medical diseases, and management modalities places it on the "severe" end of the spectrum of acute pancreatitis. For many reasons the group of patients studied is heavily weighted toward that sub-group of acute pancreatitis which is handled surgically, and does not
Biliary Alcohol Traumatic
Hyperlipoproteinemia (Type IV) Postoperative Carcinoma of Pancreas Idiopathic
Died
Total
15 8 5 2 3 1 3
3 1 1
18 (39%) 9 (20%) 6 (13%) 2 ( 4%) 3 ( 7%) 2 ( 4%) 6 (13%)
1 3
Mortality
Incidence
7/46 (15%) 6/41 (15%)
4/7 (57%) 3/6 (50o)
13/46 (28%) 8/13 (62%) 9/50 (18%) 5/9 (55%)
19/306 (6%) 10/31 (32%)
Studies
Survived
Mortality
Incidence
18/83 (22%) 8/18 (44%)
4-5 days prior to use of parenteral nutrition. The diagnosis was established by each patient meeting at least two of the following three criteria: (1.) A clinical syndrome of abdominal pain and/or vomiting and epigastric tenderness (46 out of 46 patients). (2.) Increased serum level of amylase greater than 25 Russell units or lipase greater than one unit/ml (43 out of 46 patients) and/or increased ratio of amylase clearance to creatinine clearance (17 out of 29 patients).27 (3.) Operative or pathologic findings consistent with the diagnosis of acute pancreatitis (37 out of 46 patients). Of the 44 patients studied, 21 were male and 23 were female. Their age range was from 8 to 90 years. There were 10 patients treated in 1972, 17 in 1973, and 17 in 1974. The details of the composition of the parenteral hyperalimentation solutions and administration have been described elsewhere.1 7'22 Six patients with renal failure complicating their hospital course were treated with essential amino acids and hypertonic dextrose.1
TABLE 2. Mortality by Etiology of Pancreatitis
Respiratory Failure
18/19 (95%) 6/10 (60o)
12/31 (39o) 9/12 (75%)
Surgical Mortality
8/36 (22%) 9/16 (56%) 36/211 (17%) 10/21 (48%) 4/16 (26%)
illustrate a representative cross-section of the patients who present with pancreatitis. Our experience overall has been that approximately 70o of those with acute pancreatitis have alcohol ingestion as the principal underlying etiologic agent and 80%o have no operative intervention during their hospital course. The large percentage of patients in this series treated operatively does not suggest differences in indications for operative intervention as much as selection of patients for hyperalimentation because of the relative severity of their illness. Biliary tract disease was the etiology of pancreatitis in 39% (18 of 46 of our patients), alcohol in less than 20% (6 of 46). Postoperative pancreatitis (three of 46) followed caesarian section, transduodenal sphincteroplasty for recurrent common duct stones, and excision and grafting of an abdominal aortic aneurysm. Carcinoma of the pancreas (two of 46) presented with the syndrome of recurrent epigastric pain, elevated pancreatic enzymes and volume requirement. Laparotomy was required in both cases to establish the diagnosis. The category of traumatic pancreatitis (6 of 46) might well be considered with the postoperative group as all required emergency surgery after their primary injury. Pancreatitis persisted in the postoperative course but in all 6, was thought etiologically related to the trauma. All 6 initial procedures were for control of intraabdominal bleeding but two involved repair of a pancreatic laceration and one distal pancreatectomy. The contribution of etiology of pancreatitis to ultimate mortality is illustrated in Table 2. Four of the 46 patients in this group had uncomplicated past medical histories. The vast majority had complicating underlying illnesses which further jeopardized their survival capacity when faced with the stress of acute pancreatitis. These concomittant medical problems are summarized in Table 3. Management
Non-Operative The multiplicity of modalities which exist for the therapy of pancreatitis was reflected in the various
Vol. 186. No. 5
653
PARENTERAL NUTRITION IN PANCREATITIS
regimens used in these patients. All but two had nasogastric tubes placed (44 out of 46). Seventy per cent of the patients were placed on "6prophylactic" antibiotics. The choices of specific agents reflected an attempt at broad spectrum coverage and included various regimens. Ampicillin or cephalothin was used alone in 18 patients. In 8 additional cases the combination of penicillin and chloramphenicol or clindamycin and an aminoglycoside was chosen. No statement can be made as to the incidence of septic complications with these regimens but certainly none of the antibiotic umbrellas completely prevented wound infection or septicemia in these patients. Volume requirement was dealt with appropriately with heavy reliance on colloid. Seventy-four per cent of these patients required blood transfusions during the course of their illness. Forty-one per cent received two to 10 units while 20o received greater than 10 units of blood. Salt poor albumin and furosemide were used in 6 patients with pulmonary edema and pancreatitis but results were equivocal. Two patients seemed to respond rapidly to this regimen but two resolved their pulmonary problems over 5-7 days and two clearly deteriorated on this therapy. Cardioactive drugs were used in 25% of all patients for complications of low cardiac output. Digitalization was carried out acutely in 8 patients and 7 required vasoactive amines to maintain their cardiac output. One patient was treated for a brief period with an intra-aortic balloon pump with TABLE 3. Associated Medical Problems at Time of Presentation with Pancreatitis (46 Patients)
Cardiovascular Disease (including angina, valvular disease and arrythmias requiring outpatient medication) Pulmonary Disease COPD Pneumonia Pleural effusion Active TB
Acute/Chronic Alcoholism Delirium Tremens
Significant Liver Disease Biopsy confirmed cirrhosis Viral hepatitis Status-post portocaval shunt Significant Renal Disease (BUN > 36, Creatinine > 2.0) Anuria Other Duodenal ulcer Cerebrovascular 5 disease accident Diabetes Mellitus 5 Sjogren's Syndrome with cryoGI bleeding globulinemia Porphyria Multiple Sclerosis
6 3
2 I
12 2
3
2
TABLE 4. Operative Procedures During Hospital Course for Pancreatitis Survival by Procedure
GU reconstruction and small bowel resection 3-Tube placement (15) External drainage of pancreatic pseudocyst or abscess Distal pancreatectomy Cholecystectomy Cholecystostomy CDE Pancreatic cystogastrostomy Splenectomy Puestow procedure Transduodenal sphincterotomy and sphincteroplasty Dilatation of papilla Repair of pancreatic laceration By-pass procedure for pancreatic carcinoma
No. of Patients
Survived
Died
1 9
1 4
0 5
8 3 11 3 11 6 1 2
4 3 9 2 9 1 1 2
4 0 2 1 2 5 0 0
0 1 1
7 1 0
1 0 1
2
2
0
initial success in dealing with cardiac dysfunction only to fall victim to late cardiac arrest. Large doses of corticosteroids were given to three patients whose initial course suggested a septic component to their presenting shock (two of the three patients survived). Peritoneal dialysis was used in the therapy of 6 patients and atropine was used in only one. Glucagon and trasylol were not used in any of the patients in this series. There were 10 patients (22%) who were treated completely nonoperatively. In this sub-group there was only one death. The immediate cause of death of this patient was acute renal failure and intractable cerebral edema. Operative Treatment Indications for operation in these cases of acute pancreatitis were: (1) Deterioration or failure to improve on an
"optimal medical program". (2) Clinical
suspicion of biliary disease, pancreatic carcinoma or pancreatic pseudocyst/abscess as the etiology of the acute pancreatitis. (3) Complication of the course of acute pancreatitis with sepsis from an apparent intraabdominal source or intra-abdominal bleeding. (4) Therapy of relapsing pancreatitis. Because of the variability of intra-abdominal pathology, the clinical setting and individual experience, multiple procedures were often required at a single operative venture. The variety and frequency of these procedures is illustrated in Table 4. Six patients had two operations during the course of their hospital stay with four requiring redrainage of intra-abdominal abscesses, one requiring re-exploration for bleeding
GOODGAME AND FISCHER
654 15r
Iz
Ann. Surg.
November 1977
* Total Number of Patients Ea Number of Patients Dying After This Period of TPN
10F FIG. 1. Duration of G.I. dysfunction and inability to take oral nourishment as indicated by duration of parenteral nutrition had no effect on the mortality of the illness.
LA.
0
z
9
5F
u
n1
1-10
11-20
21-30
31-40
Ifl I|
In
51-60 DAYS OF TPN
61-70
41-50
immediately postoperatively, and one requiring a gastrojejunostomy for chronic duodenal obstruction secondary to pancreatitis. Of these 6 patients, two died and four were discharged. Of the total operative group of 36 patients, eight (22%) died and 28 (77%) were discharged. Of the 8 patients who died, two died in intractable septic shock, two died of combined cardiac, pulmonary and renal failure, and one succumbed to an acute myocardial infarction secondary to septic hypotension following a T-tube cholangiogram. The other three patients died of pulmonary embolism, pulmonary insufficiency, and acute renal failure with terminal candida sepsis. Hyperalimentation and Hospital Course
Despite the overall severity of acute pancreatitis and the multiplicity of underlying medical problems in this group, the technical features of hyperalimentation offered few problems. Ninety-nine catheters were placed with only three mechanical complications. There was one episode of subclavian artery puncture which required no specific therapy and one episode of subcutaneous infiltration of hyperalimentation solution secondary to inadequate fixation of the administration catheter. Neither of these complications added to inhospital time. One patient developed subclavian vein thrombosis noted two weeks after discharge after complaints of arm swelling prompted a venogram. This required 6 weeks of anticoagulation for resolution. Duration of hyperalimentation varied from five to 90
I
71-80
81-90
days with an average of 28 days per patient. When the 46 patients are divided into two groups according to the length of time they required parenteral nutrition (Fig. 1), those who were unable to eat for more than one month did no worse in terms of survival than those whose disease resolved in less than 30 days. Much of this similarity may be explainable on the basis of more severe disease present in those who died early in their course, but nutritional support certainly contributed to the progress of the group of severely ill patients unable to take oral alimentation for 50 to 90 days. Parenteral nutrition was discontinued after oral intake was adequate in 33 of the 46 patients studied. Five patients were hyperalimented until their death and two patients had their I.V. nutrition discontinued when hope for their recovery was lost. Six patients had their hyperalimentation discontinued because of complications directly related to that modality of therapy. Episodes of catheter-related sepsis prompted discontinuation in five patients while inability to control rising serum potassium was given as the reason for stopping parenteral nutrition in one other. Despite the relative metabolic chaos resulting from pancreatitis itself and the 15% incidence of acute renal failure, there were only four episodes of metabolic abnormalities which required discontinuation of hyperalimentation. Initial glucose intolerance was common (25%) but was usually controlled by temporarily reducing the infusion rate or by incorporating small amounts (10-20 units) of regular insulin to the infusion mixture. There was only one patient in whom glucose
Vol. 186 . No. 5
PARENTERAL N UTR1I TIO N IN PANCREATITIS -
.
.
v.
I.,
-
-
-
intolerance posed a significant problem. This eventually required 60 units of regular insulin per liter of hyperalimentation solution to maintain a blood glucose of less than 200 mg per 100 milliliters. There were two episodes of protein intolerance with elevation of serum ammonia. One episode occurred in a patient with a previous portacaval shunt. The second occurred in a patient with persistent bacteremia secondary to undrained intra-abdominal abscesses who finally succumbed to cardiovascular collapse related to her prolonged sepsis. Electrolyte abnormalities were common in this population but usually responded to manipulation of the content of the hyperalimentation mixtures. Of particular interest was hypocalcemia ( 50, Creatinine > 3.5, urine output 75 with normal creatinine & urine output)
2
Metabolic
New onset glucose intolerance requiring insulin
Hyperammonemia Hypokalemia Hypocalcemia Encephalopathy Surgical Complications (36 patients required operation) Wound infections Wound dehiscence Recurrent intrabdominal abscess Fistulas Re-exploration for bleeding Duodenal obstruction requiring reoperation post-sphincteroplasty Bleeding Dyscrasia
7 2 1 7 1
3 1 1 1 -
16 13 2 4 3 1
4 3 3 1
2
18% to 39o. The mortality associated with this complication ranges from 44% to 75%. There is no improvement in these parameters in this series of hyperalimented patients with an incidence of respiratory failure of 28% and a mortality associated with this complication of 62%. Renal abnormalities affected 9 patients and ranged from simple pre-renal azotemia in two patients, to acute renal failure (BUN >50, creatinine >3.5, urine output
